Involvement of Pattern Recognition Receptors in the Direct Influence of Bacterial Components and Standard Antiacne Compounds on Human Sebaceous Gland Cells

Skin Pharmacol Physiol. 2021;34(1):19-29. doi: 10.1159/000513259. Epub 2021 Feb 18.

Abstract

Introduction: Pattern recognition receptors are involved in innate and adaptive immunity by detecting microbial components. Bacteria have been accused to play a role in inflammatory acne. We investigated the potential involvement of Toll-like receptor (TLR)2, TLR4, TLR6, and CD14 in the direct influence of bacterial components and standard antiacne compounds on human sebocytes.

Methods: mRNA and protein expression of TLR2, TLR4, TLR6, and CD14 in SZ95 sebocytes was evaluated by real-time qRT-PCR and immunocytochemistry. The effects of lipopolysaccharides (LPS) and lipoteichoic acid on TLR2, TLR4, and CD14 expression and of cytokine/chemokine secretion by 13-cis-retinoic acid, all-trans-retinoic acid, retinol, and hydrocortisone at the mRNA and protein levels were assessed by real-time qRT-PCR and ELISA and verified by cocultivation with neutralizing antibodies.

Results: The constitutive expression of TLR2, TLR4, and CD14 in SZ95 sebocytes was augmented by exposure to LPS. Hydrocortisone induced TLR2, but markedly reduced TLR4 expression. 13-cis-retinoic acid and all-trans-retinoic acid regulated IL-6 release. LPS enhanced and hydrocortisone reduced cytokine and chemokine release. Anti-TLR4 and anti-CD14 mAb blocked LPS-induced IL-8 and IL-6 release.

Conclusions: Microbial components use pattern recognition receptors to directly activate sebocytes to express a wide range of proinflammatory molecules and especially IL-8 and IL-6 in a TLR4- and CD14-specific manner. Retinoids, but mostly corticosteroids, also use this pathway to exhibit anti-inflammatory effects.

Keywords: Human sebaceous gland cells; Hydrocortisone; Innate immunity; Retinoids; Toll-like receptors.

MeSH terms

  • Acne Vulgaris / drug therapy*
  • Acne Vulgaris / pathology
  • Cell Culture Techniques
  • Humans
  • Hydrocortisone / pharmacology
  • Inflammation Mediators / metabolism*
  • Isotretinoin / pharmacology
  • Lipopolysaccharide Receptors / drug effects
  • Lipopolysaccharides / pharmacology
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Retinoids / pharmacology*
  • Sebaceous Glands / drug effects*
  • Teichoic Acids / pharmacology
  • Toll-Like Receptors / drug effects*
  • Tretinoin / pharmacology
  • Vitamin A / pharmacology

Substances

  • Inflammation Mediators
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • RNA, Messenger
  • Retinoids
  • Teichoic Acids
  • Toll-Like Receptors
  • Vitamin A
  • lipoteichoic acid
  • Tretinoin
  • Isotretinoin
  • Hydrocortisone